|Publication number||US6569195 B2|
|Application number||US 09/883,870|
|Publication date||May 27, 2003|
|Filing date||Jun 18, 2001|
|Priority date||Jul 2, 1999|
|Also published as||CA2342866A1, CA2342866C, DE60032102D1, DE60032102T2, DE60042134D1, EP1107707A1, EP1107707B1, EP1757250A2, EP1757250A3, EP1757250B1, EP2092913A1, EP2292184A1, EP2292184B1, US6258121, US20010032014, WO2001001890A1|
|Publication number||09883870, 883870, US 6569195 B2, US 6569195B2, US-B2-6569195, US6569195 B2, US6569195B2|
|Inventors||Dachuan Yang, Joel L. Stanslaski, Lixiao Wang, Scott R. Smith|
|Original Assignee||Scimed Life Systems, Inc.|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (106), Non-Patent Citations (25), Referenced by (50), Classifications (23), Legal Events (3) |
|External Links: USPTO, USPTO Assignment, Espacenet|
US 6569195 B2
A stent having a polymeric coating for controllably releasing an included active agent. The polymeric coating includes a blend of a first polymeric material, which if alone, would release the agent at a first, higher rate, and a second polymeric material, which if alone would release the agent at a second, lower rate over a longer time period. One stent coating utilizes a faster releasing hydrophilic polymeric material and a slower releasing hydrophobic material. One stent coating includes a blend of a faster releasing PLA-PEO copolymer and a slower releasing PLA-PCL copolymer. One active agent is Taxol. One use of the Taxol delivering stent is to inhibit restenosis following angioplasty.
What is claimed is:
1. An implantable stent prosthesis for delivering a biologically active material to a patient comprising:
(a) a stent body having a surface adapted for exposure to body tissue of the patient;
(b) a coating disposed over at least a portion of the surface of the stent body;
wherein the coating comprises: (i) a biologically active material selected from the group consisting of anti-thrombogenic agents, anti-angiogenesis agents, anti-proliferative agents, growth factors, radiochemicals, and lovastatin; and (ii) a mixture of a first co-polymer and a second co-polymer, wherein said first co-polymer releases the biologically active material at a first rate and said second co-polymer releases the biologically active material at a second rate, wherein said second rate is slower than said first rate.
2. The stent of claim 1, wherein said first co-polymer is hydrophilic.
3. The stent of claim 1, wherein said second co-polymer is hydrophobic.
4. The stent of claim 1, wherein said first co-polymer is hydrophilic and said second co-polymer is hydrophobic.
5. The stent of claim 1, wherein said first co-polymer comprises polylactic acid/polyethylene oxide.
6. The stent of claim 1, wherein said second co-polymer comprises polylactic acid/polycaprolactone.
7. The stent of claim 1, wherein said first co-polymer includes polylactic acid/polyethylene oxide and said second co-polymer includes polylactic acid/polycaprolactone.
8. The stent of claim 7, wherein said coating comprises about 20% by weight polylactic acid/polyethylene oxide and about 80% by weight polylactic acid/polycaprolactone.
9. The stent of claim 7, wherein said coating comprises about 50% by weight polylactic acid/polyethylene oxide and about 50% by weight polylactic acid/polycaprolactone.
10. The stent of claim 1, wherein said anti-thrombogenic agent is heparin or ticlopidine.
11. The stent of claim 1, wherein said anti-angiogenesis agent is trapidil.
12. The stent of claim 1, wherein said anti-proliferative agent is selected from the group consisting of angiopeptin, colchicine, hirudin, paclitaxel, paclitaxel analogues, paclitaxel derivatives, and combinations thereof.
13. The stent of claim 1, wherein said growth factors are selected from the group consisting of VEGF, TGF-beta, IGF, PDGF, and FGF.
14. A method of making an implantable stent prosthesis for delivering a biologically active material to a patient, wherein said method comprises:
(a) providing a stent body having a surface adapted for exposure to body tissue of the patient;
(b) applying a coating over at least a portion of said surface; wherein said coating comprises: (i) a biologically active material selected from the group consisting of anti-thrombogenic agents, anti-angiogenesis agents, anti-proliferative agents, growth factors, radiochemicals, and lovastatin; and (ii) a mixture of a first co-polymer and a second co-polymer, wherein said first co-polymer releases said biologically active material at a first rate and said second co-polymer releases said biologically active material at a second rate, and wherein said second rate is slower than said first rate.
15. The method of claim 14, wherein said anti-thrombogenic agent is heparin or ticlopidine.
16. The method of claim 14, wherein said anti-angiogenesis agent is trapidil.
17. The method of claim 14, wherein said anti-proliferative agent is selected from the group consisting of angiopeptin, colchicine, hirudin, paclitaxel, paclitaxel analogues, paclitaxel derivatives, and combinations thereof.
18. The method of claim 14, wherein said growth factors are selected from the group consisting of VEGF, TGF-beta, IGF, PDGF, and FGF.
19. The method of claim 14, wherein said first co-polymer is hydrophilic.
20. The method of claim 14, wherein said second co-polymer is hydrophobic.
21. The method of claim 14, wherein said first co-polymer comprises polylactic acid/polyethylene oxide.
22. The method of claim 14, wherein said second co-polymer comprises polylactic acid/polycaprolactone.
23. The method of claim 14, wherein said first co-polymer includes polylactic acid/polyethylene oxide and said second co-polymer includes polylactic acid/polycaprolactone.
24. The method of claim 14, wherein said coating comprises about 20% by weight polylactic acid/polyethylene oxide and about 80% by weight polylactic acid/polycaprolactone.
25. The method of claim 14, wherein said coating comprises about 50% by weight polylactic acid/polyethylene oxide and about 50% by weight polylactic acid/polycaprolactone.
26. An implantable stent prosthesis for delivering a restinosis inhibiting agent to a patient comprising:
(a) a stent body having a surface adapted for exposure to body tissue of the patient;
(b) a coating disposed over at least a portion of the surface of the stent body, wherein the coating comprises:
(i) the restinosis inhibiting agent selected from the group consisting of paclitaxel, paclitaxel analogues, paclitaxel derivatives, and combinations thereof; and
(ii) a mixture of about 50% by weight of a copolymer of polylactic acid/polyethylene oxide and about 50% by weight of a copolymer of polylactic acid/polycaprolactone.
27. The implantable stent of claim 26, wherein said paclitaxel derivatives are selected from the group consisting of 2-succinyl-taxol, 2′-succinyl-taxol triethanolamine, 2′-glutaryl-taxol, 2-glutaryl-taxol triethanolamine salt, 2-O-ester with N-(dimethylaminoethyl) glutamine, and 2′-O-ester with N-(dimethylaminoethyl) glutamide hydrochloride salt.
28. An implantable stent prosthesis for delivering a biologically active material to a patient comprising:
(a) a stent body having a surface adapted for exposure to body tissue of the patient;
(b) a coating disposed over at least a portion of the surface of the stent body;
wherein the coating comprises: (i) a biologically active material selected from the group consisting of anti-thrombogenic agents, anti-angiogenesis agents, anti-proliferative agents, growth factors, radiochemicals, and lovastatin; and (ii) a mixture of a first polymer and a second polymer, wherein said first polymer releases the biologically active material at a first rate and said second polymer releases the biologically active material at a second rate, wherein said second rate is slower than said first rate.
29. The stent of claim 28, wherein said first polymer is hydrophilic.
30. The stent of claim 28, wherein said second polymer is hydrophobic.
31. The stent of claim 28, wherein said first polymer is hydrophilic and said second polymer is hydrophobic.
32. A method of making an implantable stent prosthesis for delivering a biologically active material to a patient, wherein said method comprises:
(a) providing a stent body having a surface adapted for exposure to body tissue of the patient;
(b) applying a coating over at least a portion of said surface; wherein said coating comprises: (i) a biologically active material selected from the group consisting of anti-thrombogenic agents, anti-angiogenesis agents, anti-proliferative agents, growth factors, radiochemicals, and lovastatin; and (ii) a mixture of a first polymer and a second polymer, wherein said first polymer releases said biologically active material at a first rate and said second polymer releases said biologically active material at a second rate, and wherein said second rate is slower than said first rate.
33. The method of claim 32, wherein said first polymer is hydrophilic.
34. The method of claim 33, wherein said second polymer is hydrophobic.
This application is a continuation of application Ser. No. 09/346,975 filed Jul. 2, 1999, now U.S. Pat. No. 6,258,121.
FIELD OF THE INVENTION
The present application is generally related to medical devices. More specifically, the present invention relates to stent coatings capable of releasing agents over time. In particular, the present invention includes a blend of two co-polymers adapted to release restenosis-inhibiting agents over a sustained time period.
BACKGROUND OF THE INVENTION
Vascular disease is a leading cause of death and disability in the developed world. In the United States, more than half of all deaths are due to cardiovascular disease. Atherosclerosis is the most common form of vascular disease and leads to insufficient blood supply to body organs, which can result in hearts attacks, strokes, and kidney failure. Atherosclerosis is a form of vascular injury in which the vascular smooth muscle cells in the artery wall undergo hyperproliferation and invade and spread into the inner vessel lining, which can make the vessels susceptible to complete blockage when local blood clotting occurs. This can lead to death of the tissue served by that artery. In the case of a coronary artery, this blockage can lead to myocardial infarction and death.
Coronary artery blockage can be treated with coronary artery bypass surgery and/or angioplasty. Both procedures may initially appear to be successful, but can be in effect undone by the effect of restenosis, or the recurrence of stenosis after such a treatment. Restenosis is believed to include hyperproliferation of vascular smooth muscle cells. In particular, about one third of patients treated using angioplasty have restenosis and blockage within 6 months after the procedure.
To prevent vessel blockage from restenosis, stents are used. Stents are nominally tubular structures and can have either solid walls or lattice like walls, and can be either balloon expandable or self-expanding. After angioplasty balloon dilatation, the previously constricted vessel is at least temporarily widened. A stent can be delivered on a catheter and expanded in place or allowed to expand in place against the vessel walls. With the stent in place, restenosis may or may not be inhibited, but the probability and/or degree of blockage is reduced due to the structural strength of the stent opposing the inward force of any restenosis. Restenosis may occur over the length of the stent and be at least partially opposed by the stent. Restenosis may also occur past the ends of the stent, where the inward forces of the stenosis are unopposed.
Therapeutic agents to inhibit restenosis have been used with varying success. Taxol, an antimicrotubule agent isolated from the bark of the western Pacific Yew tree, is especially effective in inhibiting some cancers and is believed to be effective in combating restenosis. Systemic administration of Taxol can have undesirable side effects, making local administration a preferred mode of treatment.
Local administration of Taxol may be more effective when carried out over a longer time period, such as a time period at least matching the normal reaction time of the body to the angioplasty. At the same time, it may be desirable to provide an initial high dosage of Taxol over an initial period. Local administration of Taxol over a period of days or even months may be most effective in inhibiting restenosis.
Controlled release of therapeutic agents can utilize various technologies. Devices are known having a monolithic layer or coating incorporating a heterogeneous solution and/or dispersion of an active agent in a polymeric substance, where the diffusion of the agent is rate limiting, as the agent diffuses through the polymer to the polymer-fluid interface and is released into the surrounding fluid. In some devices, a soluble substance is also dissolved or dispersed in the polymeric material, such that additional pores or channels are left after the material dissolves. A matrix device is generally diffusion limited as well, but with the channels or other internal geometry of the device also playing a role in releasing the agent to the fluid. The channels can be pre-existing channels or channels left behind by released agent or other soluble substances.
Erodible or degradable devices typically have the active agent physically immobilized in the polymer. The active agent can be dissolved and/or dispersed throughout the polymeric material. The polymeric material is often hydrolytically degraded over time through hydrolysis of labile bonds, allowing the polymer to erode into the fluid, releasing the active agent into the fluid. Hydrophilic polymers have a generally faster rate of erosion relative to hydrophobic polymers. Hydrophobic polymers are believed to have almost purely surface diffusion of active agent, having erosion from the surface inwards. Hydrophilic polymers are believed to allow water to penetrate the surface of the polymer, allowing hydrolysis of labile bonds beneath the surface, which can lead to homogeneous or bulk erosion of polymer.
What would be desirable is a stent coating capable of releasing a therapeutic agent over a sustained time period. What would be advantageous is a stent coating able to release an agent over approximately the same time period as the need for the therapeutic agent. A method for controlling the dosage rate and period of an active agent by controlling the composition of a stent coating would also be advantageous.
SUMMARY OF THE INVENTION
The present invention includes a stent having a stent body, a coating disposed over at least a portion of the body, and an active agent releasably dispersed in at least part or portion of the coating. A preferred active agent is paclitaxel, analogues, derivatives, and combinations thereof. The coating can include a blend of a first co-polymer having a first, high release rate and a second co-polymer having a second, lower release rate relative to the first release rate. The first and second copolymers are preferably erodible or biodegradable. In one embodiment, the first copolymer is more hydrophilic than the second copolymer. In one embodiment, the first copolymer includes a polylactic acid/polyethylene oxide (PLA-PEO) copolymer and the second copolymer includes a polylactic acid/polycaprolactone (PLA-PCL) copolymer.
The relative amounts and dosage rates of active agent delivered over time can be controlled by controlling the relative amounts of the faster releasing polymers relative to the slower releasing polymers. For higher initial release rates the proportion of faster releasing polymer can be increased relative to the slower releasing polymer. If most of the dosage is desired to be released over a long time period, most of the polymer can be the slower releasing polymer. The stent can be coated by spraying the stent with a solution or dispersion of polymer, active agent, and solvent. The solvent can be evaporated, leaving a coating of polymer and active agent. The active agent can be dissolved and/or dispersed in the polymer. In some embodiments, the co-polymers can be extruded over the stent body.
In use, the stent can be put into position in a body vessel such as a coronary vessel after a procedure such as angioplasty. The stent can be left in position, and the erodible or biodegradable coating allowed to degrade. As the polymeric coating degrades, the active agent can absorb into the vessel walls.
DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a stent in accordance with an exemplary embodiment of the present invention;
FIG. 2 is a perspective view of a further preferred stent in accordance with the present invention; and
FIG. 3 is a magnified, partial plan view of the stent of FIG. 1, illustrating the polymeric coating of the present invention disposed thereon.
DETAILED DESCRIPTION OF THE INVENTION
The present invention includes a stent having a polymeric coating for delivering a biologically active agent or other therapeutic substance over a target time period. The polymeric coat includes a first polymer and a second polymer, where the first polymer alone would release the active agent at a faster rate than the second polymer would alone, and thus, deplete the active agent immobilized by the first polymer in a shorter time relative to the second polymer. In preferred embodiments, the first polymer is hydrophilic and the second polymer is hydrophobic.
Referring now to the drawings wherein like reference numerals refer to like elements throughout the several views, FIG. 1 shows a perspective view of a stent 10, in a non-expanded form, in accordance with the present invention. The skeletal frame of the stent 10 preferably includes wire-like members 12 forming a distinct, repetitive serpentine pattern. This repetitive serpentine pattern consists of multiple U-shaped curves 14. The areas within the U-shaped curves 14 are open 16. With no recognizable beginning or end to this serpentine pattern, wire 12 forms expandable serpentine element 18. Serpentine elements 18 are arranged along the longitudinal axis of the stent 10 so that the U-shaped curves 14 of abutting serpentine elements 16 may be joined through an interconnecting element 20. Through the interconnecting elements 20, a continuous wire 12 framework is created between multiple serpentine elements 18 forming the stent 10.
FIG. 2 shows a perspective view of a further preferred stent 110 in accordance with the present invention. This stent 110, also has a continuous wire 112 framework. This framework, however, is maintained by a repetitive rectangular-patterned element 114. The areas within the rectangular wire element 114 are open 116. The rectangular wire elements 114 are aligned lengthwise in the longitudinal axis of the stent 110. Adjacent rectangular wire elements 114 are offset half the lengthwise distance of a similar rectangular wire element 114. The end of the stent is formed by the full completion of one rectangular wire element 114, and the subsequent open end of the adjacent rectangular wire element 122. Thus, the ends of the stent possess an alternating open-closed wire configuration.
These stents are exemplary of stents which may incorporate the present invention. These, and other suitable stents are disclosed in U.S. patent application Ser. No. 08/874,190, filed Jun. 13, 1997, entitled “Polymeric Layered Stent”, of which the disclosure is incorporated herein by reference.
The term “wire”, as used in describing the frame material, should not be mistaken as being limited to metallic materials. In fact, the “wire” forming the stents 10 & 110 may consist of any biocompatable material possessing the structural and mechanical attributes necessary for supporting a diseased vessel. Thus, both metallic and polymeric materials are suitable. Examples of preferred biocompatable metallic materials include stainless steel, tantalum, nitinol, and gold. Preferred polymeric materials may be selected from the list immediately below, which is not exhaustive:
poly(L-lactide) (PLLA), poly(D,L-lactide) (PLA), polyglycolide (PGA), poly(L-lactide-co-D,L-lactide) (PLLA/PLA), poly(L-lactide-co-glycolide) (PLLA/PGA), poly(D, L-lactide-co-glycolide) (PLA/PGA), poly(glycolide-co-trimethylene carbonate) (PGA/PTMC), polyethylene oxide (PEO), polydioxanone (PDS), polycaprolactone (PCL), polyhydroxylbutyrate (PHBT), poly(phosphazene), polyD,L-lactide-co-caprolactone) (PLA/PCL), poly(glycolide-co-caprolactone) (PGA/PCL), polyanhydrides (PAN), poly(ortho esters), poly(phoshate ester), poly(amino acid), poly(hydroxy butyrate), polyacrylate, polyacrylamid, poly(hydroxyethyl methacrylate), elastin polypeptide co-polymer, polyurethane, polysiloxane and their copolymers.
The skeletal framework of the stents may be formed through various methods as well. The framework may be welded, molded, or consist of filaments or fibers which are wound or braided together in order to form a continuous structure.
Often it is beneficial to both stent and treat the localized area of a diseased vessel. A therapeutic agent, therefore, can be incorporated into a polymer and applied to the stent 10 as a polymeric surface treatment. The incorporation of a therapeutic agent into a surface treatment greatly enhances the scope of this medical device by transforming the stent into a drug-delivery system. Drugs and treatments which utilize anti-thrombogenic agents, anti-angiogenesis agents, anti-proliferative agents, growth factors, and radiochemicals may be readily deployed from within the matrix of the polymeric surface treatment. Specific examples of preferred therapeutic agents include angiopeptin, colchicine, lovastatin, trapidil, ticlopidine, hirudin, Taxol, heparin, and growth factors VEGF, TGF-beta, IGF, PDGF, and FGF.
The application of such a surface treatment is generally accomplished through either a dipping or spraying process. For either process, a solvent carrier is preferred in order to incorporate the therapeutic agent within the polymer matrix. The applied mixture preferably comprises a solvent, a polymer, and a therapeutic agent, with subsequent evaporation of the solvent to leave a polymeric coating 30 as depicted in FIG. 3.
As previously stated, the present invention is directed to a polymeric coating incorporating a releasable therapeutic agent, wherein upon implantation the rate and duration of the agent is controlled to selected parameters which optimize treatment. It has been found that selected ratios of a mixture of a hydrophilic polymer and a hydrophobic polymer provide desired control of drug release.
In a preferred embodiment, the hydrophilic polymer includes a co-polymer of polylactic acid (PLA) and polyethylene oxide (PEO). In a preferred embodiment, the second polymer includes a co-polymer of polylactic acid (PLA) and poly(caprolactone) (PCL). The PLA-PEO copolymer is hydrophilic and erodes faster relative to a similar hydrophobic polymer in the body environment where the coated stent is positioned. The PLA-PCL copolymer is hydrophobic, and degrades more slowly than a comparable hydrophilic polymer. In a preferred embodiment, the polymer coating is formed of a blend of PLA-PCL and PLA-PEO. In preferred embodiments, the hydrophilic polymer has a molecular weight of greater than about 10,000 (Mn) and the second polymer has a molecular weight of greater than about 20,000 (Mn).
Formation of PLA-PEO copolymers is well known to those skilled in the art. See for example, U.S. Patent Nos. 5,476,909 and 5,548,035, herein incorporated by reference. Formation of PLA-PCL copolymers is also known to those skilled in the art. See for example, U.S. Pat. No. 5,470,829, herein incorporated by reference.
One preferred embodiment includes about 20% by weight PLA-PEO and about 80% by weight PLA-PCL copolymers. Another embodiment includes about 50% by weight PLA-PEO copolymer and about 50% by weight PLA-PCL copolymer. The embodiment having about 20% PLA-PEO and 80% PLA-PCL delivers the active agent over a longer time period, but with a lower initial release, relative to the embodiment having the 50%/50% PLA-PEO/PLA-PCL combination. The relative amounts of PLA-PEO and PLA-PCL can be adjusted to achieve the desired combination of high initial dosage rate and subsequent lower but longer lasting dosage rate.
In one preferred embodiment, the active agent or therapeutic substance is a restenosis-inhibiting agent. A preferred restenosis-inhibiting agent includes a microtubule stabilizing agent such as Taxol, paclitaxel, analogues, derivatives, and mixtures thereof. For example, derivatives believed suitable for use in the present invention include 2′-succinyl-taxol, 2′-succinyl-taxol triethanolamine, 2′-glutaryl-taxol, 2′-glutaryl-taxol triethanolamine salt, 2′-O-ester with N-(dimethylaminoethyl) glutamine, and 2′-O-ester with N-(dimethylaminoethyl) glutamide hydrochloride salt.
The Taxol can be dissolved or dispersed in the polymeric materials and the polymeric materials adhered to the stent body. In embodiments having a blended combination of PLA-PEO and PLA-PCL, the polymeric combination can be sprayed, dipped or extruded onto the stent.
The polymeric coating of the present invention can be used with various stents. A preferred use for the coating is for coronary stents. The stents can be used following angioplasty to inhibit restenosis. The stent body can serve to hold the vessel open against any restenosis and to deliver the restenosis-inhibiting agent. In one embodiment, the coating is substantially continuous over the stent body. In another embodiment, the coating is primarily over the stent structure but not over the apertures. For example, in a stent formed of a wire mesh, the coating can closely adhere to the wires without covering the apertures therebetween.
In use, a stent according to the present invention can be selected according to desired release dosage profile and provided to the treating physician. After an angioplasty procedure, the coated stent having the restenosis-inhibiting active agent can be delivered to the stenosed, recently dilated coronary artery region. Delivery can be accomplished using methods well known to those skilled in the art, such as mounting the stent on an inflatable balloon disposed at the distal end of a catheter. With the stent advanced into position near the dilated region, the stent can be forced outward and into position against the inner vessel walls. If the stent is self-expanding, the stent can be delivered by deploying the stent from within a delivery device, allowing the stent to expand against the inner vessel walls. The active agent, as it is released from the eroding polymeric coating, can be absorbed by the inner vessel walls. Over time, the polymeric coating is eroded by bodily fluids.
Numerous advantages of the invention covered by this document have been set forth in the foregoing description. It will be understood, however, that this disclosure is, in many respects, only illustrative. Changes may be made in details, particularly in matters of shape, size, and arrangement of parts, without exceeding the scope of the invention. The inventions's scope is, of course, defined in the language in which the appended claims are expressed.
|Cited Patent||Filing date||Publication date||Applicant||Title|
|US3663288||Sep 4, 1969||May 16, 1972||American Cyanamid Co||Physiologically acceptible elastomeric article|
|US3779792||Mar 8, 1971||Dec 18, 1973||Ceskoslovenska Akademie Ved||Method of protecting glass against fogging|
|US4047957||Feb 6, 1976||Sep 13, 1977||Agfa-Gevaert N.V.||Process of hardening protein-containing photographic layers with a mixture of a carboxyl group-activating, low molecular weight compound and a carboxyl group-activating polymer|
|US4100309||Aug 8, 1977||Jul 11, 1978||Biosearch Medical Products, Inc.||Coated substrate having a low coefficient of friction hydrophilic coating and a method of making the same|
|US4119094||Mar 23, 1978||Oct 10, 1978||Biosearch Medical Products Inc.||Coated substrate having a low coefficient of friction hydrophilic coating and a method of making the same|
|US4263188||May 23, 1979||Apr 21, 1981||Verbatim Corporation||Aqueous coating composition and method|
|US4306998||Jul 8, 1980||Dec 22, 1981||Bayer Aktiengesellschaft||Process for the preparation of stable aqueous dispersions of oligourethanes or polyurethanes and their use as coating compounds for flexible or rigid substrates|
|US4373009||May 18, 1981||Feb 8, 1983||International Silicone Corporation||Medical instruments; clotting inhibition|
|US4387024||Dec 13, 1979||Jun 7, 1983||Toray Industries, Inc.||Amine polymer, polyamine monomer|
|US4391797||Aug 10, 1981||Jul 5, 1983||The Children's Hospital Medical Center||Systems for the controlled release of macromolecules|
|US4459317||Apr 21, 1983||Jul 10, 1984||Astra Meditec Aktiebolag||Polysiocyanate, polyoxyethylene glycol|
|US4487808||Apr 25, 1984||Dec 11, 1984||Astra Meditec Aktiebolag||Polyetherurethane copolymers, catheters|
|US4492622||Sep 2, 1983||Jan 8, 1985||Honeywell Inc.||Clark cell with hydrophylic polymer layer|
|US4536179||Sep 24, 1982||Aug 20, 1985||University Of Minnesota||Implantable catheters with non-adherent contacting polymer surfaces|
|US4548844||Feb 11, 1985||Oct 22, 1985||Howard I. Podell||Imparts lubricant and moisture transmission properties|
|US4642267||May 6, 1985||Feb 10, 1987||Hydromer, Inc.||Thermoplastic polyurethane, polycactams|
|US4666437||Mar 5, 1986||May 19, 1987||Astra Meditec Aktiebolag||Isocyanate cured coating|
|US4675361||Jun 24, 1983||Jun 23, 1987||Thoratec Laboratories Corp.||Block copolymers, polysiloxanes, polyethers, polyureas, polyurethanes|
|US4692352||Apr 29, 1986||Sep 8, 1987||The Kendall Company||Method of making an adhesive tape|
|US4705709||Sep 25, 1985||Nov 10, 1987||Sherwood Medical Company||Lubricant composition, method of coating and a coated intubation device|
|US4721117||Apr 25, 1986||Jan 26, 1988||Advanced Cardiovascular Systems, Inc.||Torsionally stabilized guide wire with outer jacket|
|US4734092||Feb 18, 1987||Mar 29, 1988||Ivac Corporation||Ambulatory drug delivery device|
|US4748986||Jan 29, 1987||Jun 7, 1988||Advanced Cardiovascular Systems, Inc.||Floppy guide wire with opaque tip|
|US4768507||Aug 31, 1987||Sep 6, 1988||Medinnovations, Inc.||Intravascular stent and percutaneous insertion catheter system for the dilation of an arterial stenosis and the prevention of arterial restenosis|
|US4770664||Jan 17, 1985||Sep 13, 1988||Mendinvent S.A.||Casting solution of polyurethane on substrate|
|US4780352||Jul 3, 1986||Oct 25, 1988||Faricerca S.P.A.||Covering structure for absorbent hygienic-sanitary products, and an absorbent product having such a covering|
|US4833014||May 23, 1988||May 23, 1989||Aligena Ag||Composite membranes useful for the separation of organic compounds of low molecular weight from aqueous inorganic salts containing solutions|
|US4841976||Dec 17, 1987||Jun 27, 1989||Schneider-Shiley (Usa) Inc.||Steerable catheter guide|
|US4867173||Jun 30, 1986||Sep 19, 1989||Meadox Surgimed A/S||Steerable guidewire|
|US4876126||Sep 1, 1988||Oct 24, 1989||Terumo Kabushiki Kaisha||Lubricity when wetted|
|US4884579||Apr 18, 1988||Dec 5, 1989||Target Therapeutics||Catheter guide wire|
|US4923464||Sep 3, 1985||May 8, 1990||Becton, Dickinson And Company||Percutaneously deliverable intravascular reconstruction prosthesis|
|US4925698||Mar 8, 1989||May 15, 1990||Tekmat Corporation||Surface modification of polymeric materials|
|US4943460||Feb 15, 1989||Jul 24, 1990||Snyder Laboratories, Inc.||Process for coating polymer surfaces and coated products produced using such process|
|US4959074||May 25, 1988||Sep 25, 1990||Gergory Halpern||Method of hydrophilic coating of plastics|
|US4964409||Aug 31, 1989||Oct 23, 1990||Advanced Cardiovascular Systems, Inc.||Flexible hollow guiding member with means for fluid communication therethrough|
|US4969890||Jul 7, 1988||Nov 13, 1990||Nippon Zeon Co., Ltd.||Catheter|
|US4980231||Feb 15, 1989||Dec 25, 1990||Snyder Laboratories, Inc.||Wound drainage devices, surgical equipment; applying pvp and n-trimethoxypropylsily polyethylenimine to polymeric substrate slippery, durable|
|US4994071||May 22, 1989||Feb 19, 1991||Cordis Corporation||Bifurcating stent apparatus and method|
|US5002582||Dec 8, 1989||Mar 26, 1991||Bio-Metric Systems, Inc.||Natural or synthetic resins bonded through latent reactive groups|
|US5007928||May 26, 1989||Apr 16, 1991||Canon Kabushiki Kaisha||Intraocular implant having coating layer|
|US5008363||Mar 23, 1990||Apr 16, 1991||Union Carbide Chemicals And Plastics Technology Corporation||Low temperature active aliphatic aromatic polycarbodiimides|
|US5019096||Oct 14, 1988||May 28, 1991||Trustees Of Columbia University In The City Of New York||Infection-resistant compositions, medical devices and surfaces and methods for preparing and using same|
|US5026607||Jun 23, 1989||Jun 25, 1991||C. R. Bard, Inc.||Medical apparatus having protective, lubricious coating|
|US5037656||Sep 8, 1989||Aug 6, 1991||Millipore Corporation||Porous membrane having hydrophilic and cell growth promotions surface and process|
|US5037677||Nov 7, 1989||Aug 6, 1991||Gregory Halpern||Method of interlaminar grafting of coatings|
|US5040543||Jul 25, 1990||Aug 20, 1991||C. R. Bard, Inc.||Movable core guidewire|
|US5049403||Oct 12, 1989||Sep 17, 1991||Horsk Hydro A.S.||Process for the preparation of surface modified solid substrates|
|US5057371||Jun 14, 1985||Oct 15, 1991||Minnesota Mining And Manufacturing Company||Aziridine-treated articles|
|US5066705||Jan 17, 1990||Nov 19, 1991||The Glidden Company||Polycarbodiimide crosslinker|
|US5067489||Oct 26, 1990||Nov 26, 1991||Flexmedics Corporation||Flexible guide with safety tip|
|US5069217||Jul 9, 1990||Dec 3, 1991||Lake Region Manufacturing Co., Inc.||Steerable guide wire|
|US5069226||Apr 27, 1990||Dec 3, 1991||Tokin Corporation||Core of titanium, nickel alloy and overcoating|
|US5079093||Aug 9, 1989||Jan 7, 1992||Toray Industries, Inc.||Two layer polymeric coating wherein layers react with each other|
|US5080683||May 1, 1990||Jan 14, 1992||Ceskoslovenska Akademie Ved||Method for the formation of thin hydrophilic layers on the surface of objects made from non-hydrophilic methacrylate and acrylate polymers|
|US5080924||Apr 24, 1989||Jan 14, 1992||Drexel University||Method of making biocompatible, surface modified materials|
|US5084315||Feb 1, 1990||Jan 28, 1992||Becton, Dickinson And Company||Lubricious coatings, medical articles containing same and method for their preparation|
|US5091205||Dec 22, 1989||Feb 25, 1992||Union Carbide Chemicals & Plastics Technology Corporation||Coating with polyisocyanate primer and acrylic acid polymer; smoothness; medical equipment|
|US5092885||Nov 16, 1988||Mar 3, 1992||The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services||Antitumor agents, wouond healing agents, promoters of cell adhesion to prostheses|
|US5102401||Aug 22, 1990||Apr 7, 1992||Becton, Dickinson And Company||Expandable catheter having hydrophobic surface|
|US5102402||Jan 4, 1991||Apr 7, 1992||Medtronic, Inc.||Releasable coatings on balloon catheters|
|US5102417||Mar 28, 1988||Apr 7, 1992||Expandable Grafts Partnership||Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft|
|US5105010||Jun 13, 1991||Apr 14, 1992||Ppg Industries, Inc.||Hardens or cures at low temperatures|
|US5107852||Apr 2, 1990||Apr 28, 1992||W. L. Gore & Associates, Inc.||Catheter guidewire device having a covering of fluoropolymer tape|
|US5128170||May 9, 1990||Jul 7, 1992||Kanegafunchi Kagaku Kogyo Kabushiki Kaisha||Acrylamide polymer modified with azide groups|
|US5129890||Feb 1, 1991||Jul 14, 1992||Cook Incorporated||Hydrophilically coated flexible wire guide|
|US5160790||Nov 1, 1990||Nov 3, 1992||C. R. Bard, Inc.||Lubricious hydrogel coatings|
|US5211183||Mar 31, 1992||May 18, 1993||Wilson Bruce C||Steerable memory alloy guide wires|
|US5213111||Jul 10, 1991||May 25, 1993||Cook Incorporated||Composite wire guide construction|
|US5217026||Apr 6, 1992||Jun 8, 1993||Kingston Technologies, Inc.||Guidewires with lubricious surface and method of their production|
|US5222971||Oct 9, 1990||Jun 29, 1993||Scimed Life Systems, Inc.||Temporary stent and methods for use and manufacture|
|US5240994||Sep 13, 1991||Aug 31, 1993||Berol Nobel Ab||Surface with anionic groups reacted with polyethyleneimine substituted with nonionic hydrophilic polymer|
|US5241970||May 17, 1991||Sep 7, 1993||Wilson-Cook Medical, Inc.||Papillotome/sphincterotome procedures and a wire guide specially|
|US5243996||Jan 3, 1992||Sep 14, 1993||Cook, Incorporated||Small-diameter superelastic wire guide|
|US5250613||Sep 13, 1991||Oct 5, 1993||Berol Nobel Ab||Solid surface coated with a hydrophilic outer layer with covalently bonded biopolymers, a method of making such a surface, and a conjugate therefor|
|US5266359||Dec 20, 1991||Nov 30, 1993||Becton, Dickinson And Company||Lubricative coating composition, article and assembly containing same and method thereof|
|US5275173||Dec 1, 1992||Jan 4, 1994||Target Therapeutics, Inc.||For use within a patient's vasculature|
|US5282823||Mar 19, 1992||Feb 1, 1994||Medtronic, Inc.||Intravascular radially expandable stent|
|US5283063||Jan 31, 1992||Feb 1, 1994||Eagle Vision||Hydrogel plug with hydrophobic coating for blocking lacrimal fluid flow|
|US5290585||Jun 10, 1992||Mar 1, 1994||C. R. Bard, Inc.||Lubricious hydrogel coatings|
|US5304121||Nov 22, 1991||Apr 19, 1994||Boston Scientific Corporation||Catheter|
|US5304140||Aug 26, 1988||Apr 19, 1994||Terumo Kabushiki Kaisha||Catheter for introduction into blood vessel|
|US5324261||Dec 11, 1992||Jun 28, 1994||Medtronic, Inc.||Drug delivery balloon catheter with line of weakness|
|US5370614||Nov 19, 1993||Dec 6, 1994||Medtronic, Inc.||Method for making a drug delivery balloon catheter|
|US5380299||Aug 30, 1993||Jan 10, 1995||Med Institute, Inc.||Thrombolytic treated intravascular medical device|
|US5383928||Aug 19, 1993||Jan 24, 1995||Emory University||Cardiovascular disorders|
|US5419760||Oct 11, 1994||May 30, 1995||Pdt Systems, Inc.||Medicament dispensing stent for prevention of restenosis of a blood vessel|
|US5423885||Jul 14, 1993||Jun 13, 1995||Advanced Cardiovascular Systems, Inc.||Stent capable of attachment within a body lumen|
|US5443458||Dec 3, 1993||Aug 22, 1995||Advanced Cardiovascular Systems, Inc.||Multilayered biodegradable stent and method of manufacture|
|US5443496||Oct 15, 1993||Aug 22, 1995||Medtronic, Inc.||Intravascular radially expandable stent|
|US5447724||Nov 15, 1993||Sep 5, 1995||Harbor Medical Devices, Inc.||Has tissue exposed portion to release agent inhibiting adverse reaction to its presence; polymeric surface layer over reservoir; blood oxygenator|
|US5449372||Jun 14, 1991||Sep 12, 1995||Scimed Lifesystems, Inc.||Temporary stent and methods for use and manufacture|
|US5449382||Mar 2, 1994||Sep 12, 1995||Dayton; Michael P.||Minimally invasive bioactivated endoprosthesis for vessel repair|
|US5464650||Apr 26, 1993||Nov 7, 1995||Medtronic, Inc.||Intravascular stent and method|
|US5470829||Mar 25, 1993||Nov 28, 1995||Prisell; Per||Slow release of a growth factor or hormone|
|US5476909||Feb 7, 1994||Dec 19, 1995||Sam Yang Co., Ltd.||Triblock copolymer,end block of polylactide, polyglycolide or copolymer, middle block of succinic acid modified polyoxyethylene glycol; improved hydrogel material|
|US5512055||Sep 30, 1994||Apr 30, 1996||Leonard Bloom||Biocompatible, nonbioerodable polymeric coating into which a biologically active agent is adsorbed for sustained release|
|US5514154||Jul 28, 1994||May 7, 1996||Advanced Cardiovascular Systems, Inc.||Expandable stents|
|US5527337||Feb 22, 1994||Jun 18, 1996||Duke University||Bioabsorbable stent and method of making the same|
|US6231600 *||May 26, 1999||May 15, 2001||Scimed Life Systems, Inc.||Stents with hybrid coating for medical devices|
|US6258121 *||Jul 2, 1999||Jul 10, 2001||Scimed Life Systems, Inc.||Stent coating|
|US6287285 *||Jan 29, 1999||Sep 11, 2001||Advanced Cardiovascular Systems, Inc.||Therapeutic, diagnostic, or hydrophilic coating for an intracorporeal medical device|
|US6299604 *||Aug 20, 1999||Oct 9, 2001||Cook Incorporated||Coated implantable medical device|
|US6306166 *||Oct 14, 1998||Oct 23, 2001||Scimed Life Systems, Inc.||Loading and release of water-insoluble drugs|
|US6335029 *||Dec 3, 1998||Jan 1, 2002||Scimed Life Systems, Inc.||Polymeric coatings for controlled delivery of active agents|
|US6369039 *||Dec 3, 1998||Apr 9, 2002||Scimed Life Sytems, Inc.||Saturated solution; catheter|
|1||"A Powerful Case for LOPID," Parke-Davis, dated prior to Jan. 8, 1999.|
|2||Bartoli et al., 1990 "In Vitro and In Vivo Antitumoral Activity of Free, and Encapsulated Taxol," J. Microencapsulation 7(2):191-97.|
|3||Bruck, 1997, "Interactions of Synthetic and Natural Surfaces with Blood in the Physiological Environment," J. Biomed. Mater. Res. Symposium 8:1-21.|
|4||Cohn et al., 1988, "Biodegradable PEO/PLA Blcok Copolymers," Journal of Biomedical Materials Research 22(11):993-1009.|
|5||Cox et al., 1991, "Local Delivery of Heparin and Methotrexate Fails to Inhibit In Vivo Smooth Muscle Cell Proliferation," Supplement to Circulation Abstracts From the 64th Scientific Sessions, 84(4):II-71, Abstract No. 0284.|
|6||Cox et al., 1992, "Effect of Local Delivery of Heparin and Methotrexate on Neointimal Proliferation in Stented Porcine Coronary Arteries," Coronary Artery Disease 3(3):237-248.|
|7||Dev et al., 1993, "Kinetics of Drug Delivery to the Arterial Wall Via Polyurethane Coated Removable Nitinol Stent-Comparative Study of 2 Drugs," Circulation Abstracts From the 66th Scientific Sessions, 88(4) (Part 2):I-3, Abstract No. 1657.|
|8||Dev et al., 1993, "Kinetics of Drug Delivery to the Arterial Wall Via Polyurethane Coated Removable Nitinol Stent—Comparative Study of 2 Drugs," Circulation Abstracts From the 66th Scientific Sessions, 88(4) (Part 2):I-3, Abstract No. 1657.|
|9||Esquivel et al., 1984, "Reduced Thrombogenic Characteristics of Expanded Polytetrafluorethylene and Polyurethane Arterial Grafts After Heparin Bonding," Surgery, pp. 102-107.|
|10||Guyton et al., 1980, "Inhibition of Rat Arterial Smooth Muscle Cell Proliferation by Heparin," Circulation Research 46(5):625-634.|
|11||Jampel et al., In Vitro Release of Hydrophobic Drugs From Polyanhydride Disks, Ophthalmic Surgery, dated prior to Jan. 8, 1991.|
|12||Kawahito et al., 1994, "Heparin Coated Percutaneous Cardiopulmonary Support for the Treatment of Circulatory Collapse After Cardiac Surgery," ASAIO Journal 40(4):972-976.|
|13||Kishida et al., 1994, "Immobilization of Human Thrombomodulin onto Biomaterials," ASAIO Journal, Slide Forum-Materials 4, pp. M840-M845.|
|14||Kishida et al., 1994, "Immobilization of Human Thrombomodulin onto Biomaterials," ASAIO Journal, Slide Forum—Materials 4, pp. M840-M845.|
|15||Lambert et al., 1993, "A New Method For Arterial Drug Delivery Via Removable Stent," JACC 21(2):483A, Abstract No. 834-2.|
|16||Lambert et al., 1993, "Localized Arterial Drug Delivery from a Polymer Coated Removable Metallic Stent: Kinetics and Bioactivity of Forskolin," Circulation Abstracts from the 66th Scientific Sessions, 88(4)(Part 2):I-3, Abstract No. 1659.|
|17||Lindhardt et al., 19XX, "Differential Anticoagulant Activity of Heparin Fragments Prepared Using Microbial Heparinase," The Journal of Biological Chemistry 257(13):7310-7313.|
|18||Miyama et al., 1977, "A New Antigrhombogenic Heparinized Polymer," J. Biomed. Mater. Res. 11:251-265.|
|19||Moses et al., 1999, Inhibitors on Angiogenesis, Review, The Children's Hospital Medical Center, Boston, MA, dated prior to Jan. 8, 1999.|
|20||Nichols et al., 1984, "Effect of Heparin Bonding on Catheter-induced Fibrin Formation and Platelet Activation," Circulation 70(5):843-850.|
|21||Pitt et al., 1980, "The Design of Controlled Drug Delivery Systems Based on Biodegradable Polymers," Progress in Contraceptive Delivery Systems, MTP Press, Lancaster 1:17-18.|
|22||Sheppeck et al., 1991, "Examination of the Roles of Glycoprotein Ib and Glycoprotein Iib/IIIa in Platelet Deposition on an Artificial Surface Using Clinical Antiplatelet Agents and Monoclonal Antibody Blockage," Blood 78(3):673-680.|
|23||Tang et al., 1993, "Regression of Collagen-Induced Arthritis with Taxol, A Microtubule Stabilizer," Arthritis Rheum. 36(9)(Suppl.):42.|
|24||Whitborne, Presentation at the 2nd International Coronary Stenting Summit (Mar. 1-2, 1991).|
|25||Wilson, Internet Article dated Jan. 21, 1991, "Thromboresistant Plastic Coarding Treatment," Research Partners, Inc., 2 pages.|
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US6699281 *||Jul 18, 2002||Mar 2, 2004||Sorin Biomedica Cardio S.P.A.||Angioplasty stents|
|US6849089 *||Oct 2, 2002||Feb 1, 2005||Biotronik Mess-Und Therapiegeraete Gmbh & Co Ingenieurbuero Berlin||Implant with proliferation-inhibiting substance|
|US7147659||Oct 28, 2004||Dec 12, 2006||Cordis Neurovascular, Inc.||Expandable stent having a dissolvable portion|
|US7156871||Oct 28, 2004||Jan 2, 2007||Cordis Neurovascular, Inc.||Expandable stent having a stabilized portion|
|US7211108||Jan 23, 2004||May 1, 2007||Icon Medical Corp.||Can serve as a carrier for a very broad range of drugs, possibly including every drug presently used, being considered for use, or likely to be used in the future to inhibit stenosis|
|US7265199||Apr 10, 2001||Sep 4, 2007||Celonova Biosciences Germany Gmbh||Anticoagulant; for devices for preventing excessive cellular proliferation; wrappings for stents|
|US7329431 *||Jun 4, 2004||Feb 12, 2008||Terumo Kabushiki Kaisha||Cylindrical stent body coated with polymer layer containing a first drug, and biodegradable polymer nano- or micro-capsules containing a second drug, which is released after the first drug is released to the exterior of the stent.|
|US7344563||Mar 1, 2004||Mar 18, 2008||Sorin Biomedica Cardio S.R.L.||Angioplasty stents|
|US7396538||Sep 26, 2003||Jul 8, 2008||Endovascular Devices, Inc.||Biocompatible polymer drug release matrix comprising a thermoplastic polyurethane elastomer and drug (quinone-containing alkylating agents of a mitomycin family) incorporated into the biocompatible polymer matrix; inhibit proliferation of smooth muscle cells causing restenosis|
|US7607208||May 7, 2003||Oct 27, 2009||Sorin Biomedica Cardio S.R.L.||Method of making a medicated stent|
|US7611530||Dec 5, 2007||Nov 3, 2009||Codman & Shurtleff, Inc.||Expandable stent having removable slat members|
|US7622146 *||Nov 2, 2006||Nov 24, 2009||Advanced Cardiovascular Systems, Inc.||Coating a medical device such as a stent with a drug-containing polymer layer (e.g., ethylene-vinyl alcohol copolymer) and a formulation comprising a second polymer and a solvent; being a poor solvent for the therapeutic substance or the first polymer for preventing a significant migration of drug|
|US7638159||Aug 16, 2007||Dec 29, 2009||Boston Scientific Scimed, Inc.||for tubular interiors; biocompatability|
|US7753962 *||Jan 30, 2007||Jul 13, 2010||Medtronic Vascular, Inc.||having textured surfaces which allow stronger adhesion of coatings thereby decreasing the risk of coating delamination; closely grooves forming a geometric pattern distributed over the area to be coated with biocompatible polymeric coating ( e.g. polylactic acid); active materials e.g antibiotics|
|US7758568||May 27, 2004||Jul 20, 2010||Medtronic, Inc.||Implantable therapeutic substance delivery device|
|US7794498||Dec 3, 2004||Sep 14, 2010||Innolene Llc||Formed from a triblock polymer: polystyrene-polyisobutylene-polystyrene, processed to remove hygroscopic salts; maintains in vivo transparency in an aqueous ocular environment for at least two months|
|US7922764||Oct 10, 2007||Apr 12, 2011||Celonova Bioscience, Inc.||Bioprosthetic heart valve with polyphosphazene|
|US7946019||May 6, 2010||May 24, 2011||Sorin Biomedica Cardio S.R.L.||Process for producing a stent for angioplasty|
|US8007821||Jan 11, 2002||Aug 30, 2011||Celonova Biosciences Germany Gmbh||Substrates containing polyphosphazene as matrices and substrates containing polyphosphazene with microstructured surface|
|US8039475||Feb 27, 2007||Oct 18, 2011||Vertex Pharmaceuticals Incorporated||Co-crystals and pharmaceutical compositions comprising the same|
|US8042251||May 21, 2008||Oct 25, 2011||Boston Scientific Scimed, Inc.||Systems and methods for heating and cooling during stent crimping|
|US8057841||Feb 14, 2005||Nov 15, 2011||University Of Akron||Mechanically attached medical device coatings|
|US8101275||Mar 19, 2007||Jan 24, 2012||Celonova Biosciences, Inc.||Device based on nitinol, a process for its production, and its use|
|US8137396||May 19, 2010||Mar 20, 2012||480 Biomedical, Inc||Medical implant|
|US8147539||Dec 11, 2007||Apr 3, 2012||Boston Scientific Scimed, Inc.||Stent with a coating for delivering a therapeutic agent|
|US8313521||Nov 15, 2006||Nov 20, 2012||Cook Medical Technologies Llc||Method of delivering an implantable medical device with a bioabsorbable coating|
|US8372133||Oct 5, 2009||Feb 12, 2013||480 Biomedical, Inc.||Polymeric implant delivery system|
|US8372846||Oct 10, 2011||Feb 12, 2013||Vertex Pharmaceuticals Incorporated||Co-crystals and pharmaceutical compositions comprising the same|
|US8492546||Aug 29, 2008||Jul 23, 2013||Vertex Pharmaceuticals Incorporated||Co-crystals and pharmaceutical compositions comprising the same|
|US8512483 *||Jul 14, 2010||Aug 20, 2013||Biotronik Vi Patent Ag||Implant and method for manufacturing same|
|US8540765||Feb 9, 2012||Sep 24, 2013||480 Biomedical, Inc.||Medical implant|
|US8642063||Aug 20, 2009||Feb 4, 2014||Cook Medical Technologies Llc||Implantable medical device coatings with biodegradable elastomer and releasable taxane agent|
|US8652506||Jun 5, 2008||Feb 18, 2014||Boston Scientific Scimed, Inc.||Bio-degradable block co-polymers for controlled release|
|US8759353||Feb 27, 2008||Jun 24, 2014||Vertex Pharmaceuticals Incorporated||Co-crystals and pharmaceutical compositions comprising the same|
|US20110077732 *||Jul 14, 2010||Mar 31, 2011||Biotronik Vi Patent Ag||Implant and method for manufacturing same|
|US20130224276 *||Mar 18, 2013||Aug 29, 2013||Angiotech International Ag||Compositions and methods for coating medical implants|
|EP2340836A1||Feb 27, 2007||Jul 6, 2011||Vertex Pharmceuticals Incorporated||Co-crystals comprising VX-950 and their pharmaceutical compositions|
|EP2436682A1||Aug 29, 2008||Apr 4, 2012||Vertex Pharmceuticals Incorporated||Co-crystals and pharmaceutical compositions comprising the same|
|EP2463285A1||Feb 27, 2008||Jun 13, 2012||Vertex Pharmaceuticals Inc.||Co-crystals and pharmaceutical compositions comprising the same|
|WO2007089976A2||Jan 16, 2007||Aug 9, 2007||Boston Scient Scimed Inc||Local control of inflammation|
|WO2009076200A2||Dec 5, 2008||Jun 18, 2009||Vertex Pharma||Solid forms of 1-ethyl-3-(5-(5-fluoropyridin-3-yl)-7-(pyrimidin-2-yl)-1h-benzo[d]imidazol-2-yl)urea|
|WO2010064222A2||Nov 27, 2009||Jun 10, 2010||University College Cork, National University Of Ireland, Cork||Igf1 for myocardial repair|
|WO2010093889A2||Feb 12, 2010||Aug 19, 2010||Vertex Pharmaceuticals Incorporated||Solid forms of 2-(2, 4-difluorophenyl)-6-(1-(2,6-difluorophenyl)ureido)nicotinamide|
|WO2011061295A1||Nov 19, 2010||May 26, 2011||Blue Medical Devices Bv||Narrow profile composition-releasing expandable medical balloon catheter|
|WO2012097269A1||Jan 13, 2012||Jul 19, 2012||Vertex Pharmaceuticals Incorporated||Pyrimidine gyrase and topoisomerase iv inhibitors|
|WO2012097273A1||Jan 13, 2012||Jul 19, 2012||Vertex Pharmaceuticals Incorporated||Solid forms of gyrase inhibitor (r)-1-ethyl-3-[6-fluoro-5-[2-(1-hydroxy-1-methyl-ethyl) pyrimidin-5-yl]-7-(tetrahydrofuran-2-yl)-1h-benzimidazol-2-yl]urea|
|WO2012128854A1||Feb 8, 2012||Sep 27, 2012||Rytec Corporation||Side column configuration for overhead roll-up door assemblies|
|WO2012177707A1||Jun 20, 2012||Dec 27, 2012||Vertex Pharmaceuticals Incorporated||Phosphate esters of gyrase and topoisomerase inhibitors|
|WO2013133847A1 *||Mar 9, 2012||Sep 12, 2013||Eventions, Llc||Biodegradable supporting device|
|WO2014015105A1||Jul 18, 2013||Jan 23, 2014||Vertex Pharmaceuticals Incorporated||Solid forms of (r)-2-(5-(2-(3-ethylureido)-6-fluoro-7-(tetrahydrofuran-2-yl)-1h-benzo[d]imidazol-5-yl)pyrimidin-2-yl)propan-2-yl dihydrogen phosphate and salts thereof|
| || |
|U.S. Classification||623/1.46, 427/2.25, 427/2.21|
|International Classification||A61F2/00, A61K9/00, A61F2/06, A61L31/00, A61P35/00, A61L31/10, A61L31/16, A61F2/84, A61F2/90|
|Cooperative Classification||A61L2300/416, A61F2250/0067, A61L2300/602, A61L2300/608, A61F2/91, A61L31/16, A61L31/10, A61K9/0024|
|European Classification||A61L31/16, A61K9/00M5D, A61L31/10|
|Oct 25, 2010||FPAY||Fee payment|
Year of fee payment: 8
|Sep 26, 2006||FPAY||Fee payment|
Year of fee payment: 4
|Sep 16, 2003||CC||Certificate of correction|